Eye (1988) 2,114--122

Sorsby's Pseudoinfiammatory Macula Dystrophy­ Sorsby's Fundus Dystrophies

M. R. C. CAPON,' P. 1. POLKINGHORNE,* F. W. FITZKEt and A. C. BIRD* London

Summary The findings are presented on the updated Kempster pedigree with Sorsby's fundus dystrophy. The study confirms the features described in other families: autosomal dominant inheritance with complete penetrance, loss of central vision due to sub­ foveal ingrowth of new vessels, and progressive peripheral chorioretinal atrophy. By contrast to other reports the family in the current study have peripheral retinal dysfunction, a deposit of a subretinal yellow material throughout the fundus and a tritan colour defect, all prior to the loss of central vision; in some patients there was loss of central vision from atrophic disease, rather than from ingrowth of subretinal new vessels; and, there was a different temporal progression of the central subretinal neovascular complex. These features suggest the possibility of genetic heterogeneity.

In 1949 Sorsby described a progressive fundus In 1971 Fraser and Wallace described a ped­ disorder which had three key features.! The igree with similar features;4 subsequent infor­ inheritance was autosomal dominant, there mation has shown these patients to be a was bilateral loss of central vision in the fifth branch of the Randall family.5 Some of the decade of life from subretinal neovascularisa­ asymptomatic progeny had a deu­ tion, and progressive atrophy of the periph­ teranomalous defect, raising the possibility of eral choroid and retina leading to loss of a functional deficit prior to the onset of an ambulatory vision by the seventh decade in observed fundus change. most cases. The disorder was reported in five Hoskin and others published their findings families who had a widespread distribution: on an updated pedigree of the Ewbank family the Carvers came from Cumbria, the Kemp­ in 1981.6 Prior to any reduction of central sters and Randalls from London, and the acuity in this family, the authors found fine Ewbanks from the southeast England. The drusen in some patients, and in others a con­ histopathology on the Cranston sisters has fluent deposit of yellow subretinal material at been described,2 but dominant inheritance the macula. There was no colour vision abnor­ was never proven so that some doubt must mality at this stage. They concluded that these remain about the diagnosis. The peripheral anatomical changes were reliable markers of chorioretinal atrophy which occurred in all the abnormal genotype. families has been overlooked more recently In this paper the fundus findings of an and the condition was called a macular dystro­ updated pedigree of the Kempster family are phy by Duke Elder and Perkins.3 presented. Certain features described here

• Professorial Unit, Department of Clinical Ophthalmology, Moorfields Eye Hospital, City Road, London EC1V2PD. t Department of Visual Science, Institute of Ophthalmology, Judd Street, London WC1H 9QS. Correspondence: Professor A. C. Bird, FRCS, Department of Clinical Ophthalmology, Moorfields Eye Hos­ pital, City Road, London EC1V2PD. ' SORSBY S PSEUDOINFLAMMATORY MACULA DYSTROPHY 115

Fig.1. Kempster family pedigree. 0, 0 unaffected female, male;., • affected female, male; x patient examined in this study. differ from other descriptions and imply poss­ both fundi. Psychophysical testing (dark ible genetic heterogeneity. adaptation, static perimetry and fine matrix perimetry) was undertaken on two of the Materials and Methods three affected patients with good central This study describes 37 previously unreported vision in one or both eyes. Dark adaptation descendants of the Kempster familyl (Fig. 1). and static perimetry were performed using an These patients were reviewed over a period of automated modified Lister perimeter as 2 to 12 years and agreed to participate in described by Ernst et aU This apparatus uses further study: those at risk of having the red and green stimuli which enables separa­ abnormal genotype or who had lost vision in tion of the relative contributions of rods and one eye were investigated by fluorescein cones. Dark adaptation was evaluated at 25° angiography and Panel 0-15 colour vision in the nasal fieldafter a standardised two min­ assessment. ute bleach of that area. Photoreceptor sen­ Of these patients 10 were affected: seven sitivity was investigated further under had lost central vision in both eyes and two scotopic conditions using static perimetry at patIents in only one eye. The remaining mem­ multiple extramacular sites and at varying ber had good vision with deposits of drusen degrees of eccentricity and meridional arcs. and confluent yellow subretinal material in The technique elffine matrix perimetry allows 116 M. R. C. CAPON ET AL. a sensitive analysis of photoreceptor function Results within a defined area and under a predeter­ Inheritance mined background luminance.8 The appara­ In generations III and IV all affected patients tus consists of a high resolution television had an affected parent and 50 per cent of the screen which presents a matrix of pulses of children of all those with the abnormal gen­ blue light covering 7x7 degrees of arc. In the otype manifested the disease (Fig. 1). In sub­ one member of this family studied with fine sequent generations some members had not matrix perimetry scotopic conditions were reached the age at which the disease could used and a paramacular test area was chosen. become manifest. Results of all three tests are expressed in log unit elevation of threshold above normal. Night Blindness Electroretinography (ERG) and electro­ The first symptom suggesting the abnormal oculography (EO G) were performed on the genotype was difficulty with night vision. It three patients with good central vision.9 .10 occurred up to 25 years prior to the loss of

Fig.2a. ' SORSBY S PSEUDOINFLAMMATORY MACULA DYSTROPHY 117

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Fig.2. Posterior pole of patient VI8 (2a). The square, labelled ABCD, shows the area tested by fine matrix perimetry which is plotted in Fig 2b. This area includes some of the more prominent subretinal yellow material. Computerised plot of the fine matrix perimetry on patient VI8 (2b-see text for details). Log intensity of threshold is plotted on the ordinate and the retinal coordinates on the abscissa. The greater the height in the plot the greater the sensitivity loss. Points A, B, C and D correspond to those similarly labelled in figure 2a. All areas show an elevated threshold and there are abrupt changes in threshold within the test area (7" x 7") from 0.8 to 3.0 log units. central vision and was clearly recalled by 8 of Colour Defect the 10 affected patients. The dark adaptation, An asymptomatic tritan colour defect was performed in the mid periphery of the nasal found at presentation in the three patients fieldwas abnormal in the 2 patients who were (four eyes) and this persisted until loss of tested. In one patient, in whom pre-bleach central vision occurred. dark adapted thresholds were elevated above the normal mean, dark adaptation following Early Ophthalmoscopic Signs the bleach took over one hour which is about Fundus changes were always bilateral but twice the normal time. Static perimetry asymmetric. The three patients (four eyes) showed widespread increases in rod thresh­ who were seen with good vision in at least one olds with the baseline sensitivity 0.5 log units eye were examined in the fourth decade of above normal. There were regional varia­ life. At that stage these eyes had both drusen tions, with some areas having a reduction in and confluentyellow subretinal material. The sensitivity by at least 3.5 log units, the maxi­ drusen were fine and densely packed and mum measurable value of this apparatus. In could extend from the macula to the equator. the paramacular area tested with fine matrix The yellow deposit initially appeared as a perimetry, the thresholds ranged from 0.8 to 3 subtle discoloration, occurred throughout the log units above normal i.e. a 6 to 1000 fold fundus and was evident earlier in the periph­ reduction in sensitivity (Fig. 2). ery than the macula. 118 M. R. C. CAPON ET AL.

Fig. 3. Macula of patient IVI29 who retained normal central vision in both eyes (3a). Drusen are clearly visible. Within the area of yellow material there is mottled choroidal hypofluoresencetemporal to the fovea in the early part of the transit (3b). In the midperipheral fundus yellow subretinal material (3c) corresponds to the area of choroidal hypofluoresence and choroidal vessels are visible deep within this area (3d).

Similar characteristics were seen on fluor­ reduced light rise in all cases with a range from escein angiography in both the macula and 120 per cent to 165 per cent. peripheral fundus (Fig. 3) but were more marked in the latter site. Mottled choroidal hypofluorescenceoccurred in the early part of Macular Changes the eye transit (Fig. 3b and d) which corre­ Nine patients had lost central vision in one or sponded with the area of subtle yellow both eyes prior to this review. In 7 patients it material. was clear by ophthalmoscopy that the visual In the eyes with normal vision the ERGs deficitwas due to a subfoveal disciform lesion. hac) normal a and b wave amplitudes, laten­ The remaining 2 patients had choroidal atro­ cies and wave forms, using scotopic and phy at the macula but no evidence of a disci­ photopic stimuli. The EOG results showed a form reaction (Fig. 4). ' SORSBY S PSEUDOINFLAMMATORY MACULA DYSTROPHY 119 was preserved until the middle of the sixth decade oflife. One of the brothers (Fig. 4) had a long history of nyctalopia and had multiple patches of chorioretinal atrophy throughout the postequatorial fundus in addition to that at the macula.

Peripheral Chorioretinal Atrophy Progressive chorioretinal atrophy of the per­ ipheral fundus leading to social blindness occurred in five of the six patients who had reached the age of 60 years. In addition, three younger patients, still in the fifth decade of life, had identifiable peripheral fundus change. These eight patients included all who gave a history of difficulty with night vision.

Fig. 4. Macula of 60 year old patient IVI22 with count Discussion fingers vision. There is a large area of atrophy of the In this study we have presented the fundus outer retina and choroid but no evidence of subretinal findings of the updated pedigree of the neovascularisation. Similar areas of atrophy extended Kempster family. I This confirms the autoso­ out to the equatorial fundus. mal dominant inheritance pattern described originally by Sorsby and later by Hoskin,6 and In the 7 patients with subretinal neo­ in this study we have demonstrated complete vascularisation, central visual loss occurred at penetrance. Of the nine patients who lost ages ranging from 38 to 53 years. Two of the 7 central vision in one or both eyes, there was could recall a gradual loss of central vision ingrowth of subretinal new vessels beneath over several months. The disciform scars were the fovea in seven patients. We have also always large and became pigmented in the late found late peripheral chorioretinal atrophy as stages. As the scar flattened atrophy became reported by Sorsby. In the Ewbank family this the predominant feature and after several change was seen in sixty per cent of patients by decades had an appearance similar to choroi­ the age of seventy years6 and this was not dal sclerosis. Involvement of the fellow eye different to the Kempster family. occurred in most patients up to 18 months However this family study shows four fea­ after the first but one patient retained good tures which are different from those reported central vision in the second eye at the time of in other pedigrees and specifically in the last review, 3 years after losing central vision Ewbank family:6 prior to the loss of central in the first eye. The evolution of macular vision there was peripheral retinal dysfunc­ disease was closely recorded in the second eye tion in most patients and a tritan colour defect of one patient (Fig. 5). The hypofluorescence in those seen with early macular disease; the on angiography became much more marked subretinal yellow material was not limited to with time as the yellow deposit increased and the macular area but occurred throughout the the large choroidal vessels were visible deep fundus; some patients lost central vision from to this material. Occult new vessels were seen atrophic disease rather than the ingrowth of at presentation in this woman but remained subretinal new vessels; and there was a dif­ inactive for 9 months with preservation of ferent temporal progression of the subretinal good acuity until a subfoveal disciform neovascularisation leading to loss of central developed. vision. The two remaining patients who lost central vision prior to the review, had outer retinal Signs Before Central Visual Loss and choroidal atrophy involving the macula. The peripheral retinal dysfunction which was These patients were brothers, and good vision manifest as difficulty with night vision was 120 M. R. C. CAPON ET AL.

Fig. S. Posterior pole of 44 year old patient V/6 who was observed during evolution of subretinal new vessels. The area of yellow subretinal material (4a) corresponds with the area of choroidal hypofluoresence in this early part of the dye transit (4b). Large choroidal vessels are visible deep within the lesion temporal to the fovea (arrow head). Multiple areas of subretinal new vessels are seen (arrows). progressive and was symptomatic for up to 25 The electrophysiological results imply that years before loss of central acuity. The pro­ a functional defect of the retinal pigment epi­ longed dark adaptation times imply abnormal thelium occurs early in the disease. rod mediated function in the test area. Static perimetry also demonstrated abnormal rod Subretinal Yellow Material function throughout the fundus with further The yellow subretinal material was visible increases in threshold by as much as 3.0 log throughout the fundus in all the patients in the units)n local regions. Fine matrix perimetry' current study who were seen in the fourth and showed this abnormality to be present in the fifth decades of life. By contrast in the macular area and that abrupt changes in Ewbank family the yellow material was threshold occurred over a very small area. reported to be localised to the macula.6 In the These psychophysical findingsimply a diffuse older members of the Kempster family this disease process throughout the fundus but male rial was sometimes less evident. This with multiple localised areas of increased could be because the material had decreased abnormality. Further, our data suggest the in amount or that it was obscured by the per­ possibility that psychophysical tests may ipheral chorioretinal pigmentary change. Flu­ detect earlier changes in patients at a younger orescein angiography in the Kempster family age which may help to typify the metabolic demonstrated similar changes in the areas of abnormality of this disease. this deposit in the peripheral fundus to that at The presence of a tritan colour defect is not the macula (Fig. 3). These angiographic fea­ surprising in view of the known propensity for tures were also seen in the Ewbank family: the blue cone damage in early macular disease. In yellow material corresponded to the area of our study the colour defect was present when choroidal hypofluorescence during the early first tested at the time when a subtle yellow part of the dye transit but the large choroidal deposit was visible at the macula. If the func­ vessels remained visible.6 This supports tional defect was present before any Hoskin's conclusion that the hypofluores­ ophthalmoscopic change as suggested by cence could not be explained by obscuration Fraser and Wallace4 this could be used to alone but implied delayed and uneven perfu­ detect the abnormal genotype. sion of the choriocapillaris in that region. This ' SORSBY S PSEUDOINFLAMMATORY MACULA DYSTROPHY 121 may be homologous with the histologIcal cal examination of affected eyes may support observation of a widening of the intercapillary this. In addition, linkage studies offer the pillars of the choriocapillaris in the eyes of the possibility to determine if more than one gene elderly. 11 locus is involved in the transmission of the disease. Central Acuity Loss In all families described so far the disorder Neovascular ingrowth was the cause of loss of has involved not only the macula but also the central vision in 8 of 10 patients. This was peripheral fundus. This feature has been preceded in one eye by occult neovascularisa­ ignored in some of the recent descriptions tion (Fig. 5) which exhibits different growth where the disorder has been labelled a macu­ characteristics to manifest, well-defined sub­ lar dystrophy. Because of widespread fundus retinal complexes.12.13 Gradual loss of central involvement we believe that it is better termed vision in three other eyes suggests that occult a fundus dystrophy. subretinal new vessels may be common in this family. This contrasts with the rapid loss of We gratefully acknowledge the invaluable help of central vision due to manifest new vessels seen the following: (for information which completed in the Ewbank family. the family pedigree) Dr. T Walker, FRACO, Can­ The age of onset and the temporal pro­ berra, Australia; Dr. C. Pavlin, FRCS (Canada), gression of the neovascularisation at the mac­ Toronto, Canada; Dr. W. Macrae, MD, Toronto, Canada; and, in particular, Dr. M. Jay, PhD, ula is strikingly different between the Ewbank Moorfields Eye Hospital, London; (for allowing us and Kempster families.6 In the former there to see patients and have access to relevant case was precipitous loss of central vision up to notes) and to Mr. T. J. ffytche, FRCS, St Thomas' twenty years earlier than in the Kempsters Hospital, London. In addition we wish to thank the and occult neovascularisation was never seen. following colleagues at Moorfields Eye Hospital, Thus the disease in the Ewbank family is City Road, London: Mr. M. McHale, Mr. K. Sehmi characterised by the rapid onset of loss of and Miss A. Boulton, Medical Illustration Depart­ central vision at a much earlier age compared ment; (for assessment of colour vision) Mr. C. with the Kempster family. Wood, Visual Assessment Department; (for assist­ ) Atrophic macular disease without evidence ance with psychophysical testing Mr. A. T. Moore, FRCS. of choroidal neovascularisation was respon­ sible for the loss of central vision in two patients. Both retained good vision until the sixth decade of life and manifested changes References resembling that seen in geographic atrophy in 1 Sorsby A, Mason MEJ, Gardener N: A fundus dys­ the elderly. This does not exclude the possi­ trophy with unusual features. Br J Ophthalmol bility of neovascularisation having occurred at 1949,33: 67-97. 2 Ashton N and Sorsby A: Fundus dystrophy with some stage. However it is possible that the unusual features: a histological study. Br J subretinal disease alone may have induced Ophthalmol1951,35: 751-64. receptor cell and retinal pigment epithelial 3 Duke-Elder S and Perkins ES: Diseases of the uveal cell death. These findingsmay reflectvariable tract. System of Ophthalmology. London: expression of the abnormal gene in the Kimpton 1966,9: 715-19. 4 Fraser HB and Wallace DC: Sorsby's pseudoinfiam­ Kempster family and further distinguishes the matory macular dystrophy. Am J Ophthalmol disorder in this family from that reported in 1971,71: 1216-20. the Ewbank family. 5 Jay M: Personal communication. 6 Hoskin A, Bird AC, Sehmi K: Sorsby's pseu­ doinfiammatory macular dystrophy. Br J Conclusions Ophthalmol1981,65: 859-65. The differences between the manifestations of 7 Ernst W, Faulkner OJ, Hogg CR, PoweH DJ, Arden the disorder in the family in this study and the GB Vaegan, An automated static perimeter/ Ewbank family suggest the possibility of adaptometer using light emitting diodes. Br J genetic heterogeneity. Subsequent clinical Ophthalmol1983, 67: 431-42. 8 Fitzke FW: Spatial properties of scotopic sensitivity. and psychophysical assessment of these and PhD Thesis, University of London, 1986. other families with this disorder plus histologi- 9 Arden GB, Carter RM, Ernst WJK, et al.: A modi- 122 M. R. C. CAPON ET AL.

tied ERG technique and results obtained in region: a clinico-pathological study. Br J X-linked retinitis pigmentosa. Br J Ophthalmol Ophthalmol1976, 60: 324--41. 12 1982, 83: 419-30. Kies JC and Bird AC: Juxtapapillary choroidal neo­ 10 Arden GB, Barrada A, Kelsey JH: New clinical test vascularisation in the elderly. Am J Ophthalmol of retinal function based upon the standing (in press) potential of the "eye. Br J Ophthalmol1962, 46: I3 Green WR and Key SN: Senile macular degenera­ 449-67. tion: a histopathological study. Trans Am II Sarks SH: Ageing and degeneration in the macular Ophthalmol Soc 1977, 75: 180-254.